The sample of choice for measuring blood osmolality is:

• A. Serum
• B. Plasma
• C. Whole blood
• D. Serum or plasma may both be used

Answer: (D)

Measuring osmolality reflects the concentration of osmotically active particles in the extracellular fluid. Serum and plasma are both suitable because they are cell-free liquid fractions of blood that mirror this extracellular solute concentration. Whole blood contains cells with their own solutes and can vary with hematocrit; the presence of cells and potential cell lysis can distort the measurement, making it less reliable. In practice, osmolality is measured on serum or plasma using a freezing-point osmometer, and either type can be used depending on how the sample was collected (serum after clotting or plasma from anticoagulated blood). For this reason, the best answer is that serum or plasma may both be used.